Document Detail

Protective effect of metallothionein against the toxicity of cadmium and other metals(1).
MedLine Citation:
PMID:  11516518     Owner:  NLM     Status:  MEDLINE    
Metallothionein (MT) is a small-molecular weight, cysteine-rich protein that binds metals. The protective role of MT in Cd toxicity is well established but its ability to protect against toxicity of other metals remains unclear. In this study, wild-type and MT-I and -II null mice (MT-null mice) were used to determine whether MT is protective against the lethality of not only Cd but also Zn, Cu, Fe, Pb, Hg and As. Following daily subcutaneous administration of an increasing dose of each metal, starting with a low, non-toxic dose, we compared the cumulative median lethal dose (LD(50)) of each metal between wild-type and MT-null mice. The LD(50) of Cd for wild-type mice was 6.9-fold higher than for MT-null mice. The LD(50) of Zn was 2.4-fold higher for wild-type mice than for MT-null mice, and 1.4-fold higher for Cu and As. The LD(50) of Hg was 1.3-fold higher for wild-type mice than for MT-null mice, but this was not statistically significant. No difference in LD(50) values was observed between wild-type and MT-null mice following Pb and Fe administration. These results suggest that MT is an important protein in the cellular defense against Cd toxicity and lethality, but it provides much less protection against the lethality of the other metals.
J D Park; Y Liu; C D Klaassen
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicology     Volume:  163     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-08-22     Completed Date:  2001-09-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  93-100     Citation Subset:  IM    
Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160-7417, USA.
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MeSH Terms
Arsenic / toxicity
Cadmium / antagonists & inhibitors,  toxicity*
Cadmium Chloride / administration & dosage,  toxicity
Copper / toxicity
Dose-Response Relationship, Drug
Iron / toxicity
Lead / toxicity
Lethal Dose 50
Mercury / toxicity
Metallothionein / deficiency*
Metals / antagonists & inhibitors,  toxicity*
Mice, Knockout
Zinc / toxicity
Grant Support
Reg. No./Substance:
0/Metals; 10108-64-2/Cadmium Chloride; 7439-89-6/Iron; 7439-92-1/Lead; 7439-97-6/Mercury; 7440-38-2/Arsenic; 7440-43-9/Cadmium; 7440-50-8/Copper; 7440-66-6/Zinc; 9038-94-2/Metallothionein

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